RESUMO
We explored the association of Ebola virus antibody seropositivity and concentration with potential risk factors for infection. Among 1,282 adults and children from a community affected by the 2014-2016 Ebola outbreak in Sierra Leone, 8% were seropositive for virus antibodies but never experienced disease symptoms. Antibody concentration increased with age.
Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Adulto , Criança , Surtos de Doenças , Glicoproteínas , Doença pelo Vírus Ebola/epidemiologia , Humanos , Imunoglobulina G , Estudos Soroepidemiológicos , Serra Leoa/epidemiologiaRESUMO
We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (LAM) into the urine, the MTB-LAM-ELISA assay and the Determine TB-LAM-strip assay, in children with suspected tuberculosis (TB) in a high TB/HIV-prevalence setting.In a prospective study, 132 children with suspected active TB were assigned to diagnostic subgroups. Urine samples were subjected to testing by both assays to ascertain sensitivity and specificity. Host factors associated with positive LAM results were investigated and LAM excretion monitored after antituberculous treatment initiation.18 (13.6%) children had culture-confirmed pulmonary TB. The assays' sensitivity was higher in HIV-positive versus HIV-negative children: 70% (95% confidence interval 35-93%) versus 13% (0-53%) for MTB-LAM-ELISA and 50% (19-81%) versus 0% (0-37%) for Determine TB-LAM. In 35 (27%) children with excluded active TB, both assays showed a specificity of 97.1% (85-100%). Proteinuria and low body mass index were independently associated with LAM positivity. In most patients, LAM excretion declined to zero during or at conclusion of antituberculous treatment.HIV/TB co-infected children might benefit from LAM-based tests to aid early TB diagnosis and subsequent positive impact on morbidity and mortality. Using LAM as a rule-in and treatment-monitoring tool may also show further potential.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/urina , Lipopolissacarídeos/urina , Tuberculose/epidemiologia , Tuberculose/urina , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Países em Desenvolvimento , Doenças Endêmicas , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Incidência , Lipopolissacarídeos/análise , Masculino , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Escarro/microbiologia , Tanzânia/epidemiologia , Tuberculose/diagnóstico , Urinálise/métodosRESUMO
BACKGROUND: Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings. METHODS: We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin). FINDINGS: Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin. INTERPRETATION: K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally. FUNDING: Bill & Melinda Gates Foundation.
Assuntos
Mortalidade da Criança , Klebsiella pneumoniae , Humanos , Lactente , Recém-Nascido , Antibacterianos/farmacologia , Ásia Meridional/epidemiologia , Causas de Morte , Saúde da Criança , Pneumonia , Sepse , Natimorto/epidemiologia , Pré-Escolar , África Subsaariana/epidemiologiaRESUMO
BACKGROUND: Malaria is a leading cause of childhood mortality worldwide. However, accurate estimates of malaria prevalence and causality among patients who die at the country level are lacking due to the limited specificity of diagnostic tools used to attribute etiologies. Accurate estimates are crucial for prioritizing interventions and resources aimed at reducing malaria-related mortality. METHODS: Seven Child Health and Mortality Prevention Surveillance (CHAMPS) Network sites collected comprehensive data on stillbirths and children <5 years, using minimally invasive tissue sampling (MITS). A DeCoDe (Determination of Cause of Death) panel employed standardized protocols for assigning underlying, intermediate, and immediate causes of death, integrating sociodemographic, clinical, laboratory (including extensive microbiology, histopathology, and malaria testing), and verbal autopsy data. Analyses were conducted to ascertain the strength of evidence for cause of death (CoD), describe factors associated with malaria-related deaths, estimate malaria-specific mortality, and assess the proportion of preventable deaths. FINDINGS: Between December 3, 2016, and December 31, 2022, 2673 deaths underwent MITS and had a CoD attributed from four CHAMPS sites with at least 1 malaria-attributed death. No malaria-attributable deaths were documented among 891 stillbirths or 924 neonatal deaths, therefore this analysis concentrates on the remaining 858 deaths among children aged 1-59 months. Malaria was in the causal chain for 42.9% (126/294) of deaths from Sierra Leone, 31.4% (96/306) in Kenya, 18.2% (36/198) in Mozambique, 6.7% (4/60) in Mali, and 0.3% (1/292) in South Africa. Compared to non-malaria related deaths, malaria-related deaths skewed towards older infants and children (p < 0.001), with 71.0% among ages 12-59 months. Malaria was the sole infecting pathogen in 184 (70.2%) of malaria-attributed deaths, whereas bacterial and viral co-infections were identified in the causal pathway in 24·0% and 12.2% of cases, respectively. Malnutrition was found at a similar level in the causal pathway of both malaria (26.7%) and non-malaria (30.7%, p = 0.256) deaths. Less than two-thirds (164/262; 62.6%) of malaria deaths had received antimalarials prior to death. Nearly all (98·9%) malaria-related deaths were deemed preventable. INTERPRETATION: Malaria remains a significant cause of childhood mortality in the CHAMPS malaria-endemic sites. The high bacterial co-infection prevalence among malaria deaths underscores the potential benefits of antibiotics for severe malaria patients. Compared to non-malaria deaths, many of malaria-attributed deaths are preventable through accessible malaria control measures.
Assuntos
Mortalidade da Criança , Malária , Lactente , Criança , Recém-Nascido , Feminino , Gravidez , Humanos , Natimorto , Saúde da Criança , Causas de Morte , Malária/epidemiologiaRESUMO
INTRODUCTION: Determining aetiology of severe illness can be difficult, especially in settings with limited diagnostic resources, yet critical for providing life-saving care. Our objective was to describe the accuracy of antemortem clinical diagnoses in young children in high-mortality settings, compared with results of specific postmortem diagnoses obtained from Child Health and Mortality Prevention Surveillance (CHAMPS). METHODS: We analysed data collected during 2016-2022 from seven sites in Africa and South Asia. We compared antemortem clinical diagnoses from clinical records to a reference standard of postmortem diagnoses determined by expert panels at each site who reviewed the results of histopathological and microbiological testing of tissue, blood, and cerebrospinal fluid. We calculated test characteristics and 95% CIs of antemortem clinical diagnostic accuracy for the 10 most common causes of death. We classified diagnostic discrepancies as major and minor, per Goldman criteria later modified by Battle. RESULTS: CHAMPS enrolled 1454 deceased young children aged 1-59 months during the study period; 881 had available clinical records and were analysed. The median age at death was 11 months (IQR 4-21 months) and 47.3% (n=417) were female. We identified a clinicopathological discrepancy in 39.5% (n=348) of deaths; 82.3% of diagnostic errors were major. The sensitivity of clinician antemortem diagnosis ranged from 26% (95% CI 14.6% to 40.3%) for non-infectious respiratory diseases (eg, aspiration pneumonia, interstitial lung disease, etc) to 82.2% (95% CI 72.7% to 89.5%) for diarrhoeal diseases. Antemortem clinical diagnostic specificity ranged from 75.2% (95% CI 72.1% to 78.2%) for diarrhoeal diseases to 99.0% (95% CI 98.1% to 99.6%) for HIV. CONCLUSIONS: Antemortem clinical diagnostic errors were common for young children who died in areas with high childhood mortality rates. To further reduce childhood mortality in resource-limited settings, there is an urgent need to improve antemortem diagnostic capability through advances in the availability of diagnostic testing and clinical skills.
Assuntos
Causas de Morte , Erros de Diagnóstico , Humanos , Lactente , Pré-Escolar , Feminino , Masculino , Erros de Diagnóstico/estatística & dados numéricos , Autopsia , África/epidemiologia , Mortalidade da Criança , Recém-NascidoRESUMO
BACKGROUND: This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone. METHODS: In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069). FINDINGS: From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded). INTERPRETATION: Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination. FUNDING: Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
Assuntos
Vacinas contra Ebola , Ebolavirus , Doença pelo Vírus Ebola , Animais , Humanos , Lactente , Vacinas contra Ebola/efeitos adversos , Doença pelo Vírus Ebola/prevenção & controle , Serra Leoa , Guiné , Anticorpos Antivirais , Método Duplo-Cego , Glicoproteínas , FebreRESUMO
BACKGROUND: Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. METHODS: This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1-17 years were enrolled in three age cohorts (12-17 years, 4-11 years, and 1-3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. FINDINGS: From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1-3 years after placebo injection to 21% (30 of 144) of children aged 4-11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12-17 years and 4-11 years age cohorts after the first and second dose, and pyrexia in the 1-3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12-17 years (9929 ELISA units [EU]/mL [95% CI 8172-12 064]), in 119 (99%) of 120 aged 4-11 years (10 212 EU/mL [8419-12 388]), and in 118 (98%) of 121 aged 1-3 years (22 568 EU/mL [18 426-27 642]). INTERPRETATION: The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1-17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.
Assuntos
Anticorpos Antivirais/sangue , Vacinas contra Ebola/administração & dosagem , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Imunogenicidade da Vacina , Vacinas de DNA/administração & dosagem , Vacinas Virais/administração & dosagem , Adolescente , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Lactente , Injeções Intramusculares , Masculino , Serra Leoa , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologiaRESUMO
BACKGROUND: The Ebola epidemics in west Africa and the Democratic Republic of the Congo highlight an urgent need for safe and effective vaccines to prevent Ebola virus disease. We aimed to assess the safety and long-term immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in Sierra Leone, a country previously affected by Ebola. METHODS: The trial comprised two stages: an open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2. The study was done at three clinics in Kambia district, Sierra Leone. In stage 1, healthy adults (aged ≥18 years) residing in or near Kambia district, received an intramuscular injection of Ad26.ZEBOV (5 × 1010 viral particles) on day 1 (first dose) followed by an intramuscular injection of MVA-BN-Filo (1 × 108 infectious units) on day 57 (second dose). An Ad26.ZEBOV booster vaccination was offered at 2 years after the first dose to stage 1 participants. The eligibility criteria for adult participants in stage 2 were consistent with stage 1 eligibility criteria. Stage 2 participants were randomly assigned (3:1), by computer-generated block randomisation (block size of eight) via an interactive web-response system, to receive either the Ebola vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo) or an intramuscular injection of a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo on day 57 (second dose; control group). Study team personnel, except those with primary responsibility for study vaccine preparation, and participants were masked to study vaccine allocation. The primary outcome was the safety of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen, which was assessed in all participants who had received at least one dose of study vaccine. Safety was assessed as solicited local and systemic adverse events occurring in the first 7 days after each vaccination, unsolicited adverse events occurring in the first 28 days after each vaccination, and serious adverse events or immediate reportable events occurring up to each participant's last study visit. Secondary outcomes were to assess Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second vaccine in a per-protocol set of participants (ie, those who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response) and to assess the safety and tolerability of the Ad26.ZEBOV booster vaccination in stage 1 participants who had received the booster dose. This study is registered at ClinicalTrials.gov, NCT02509494. FINDINGS: Between Sept 30, 2015, and Oct 19, 2016, 443 participants (43 in stage 1 and 400 in stage 2) were enrolled; 341 participants assigned to receive the Ad26.ZEBOV and MVA-BN-Filo regimen and 102 participants assigned to receive the MenACWY and placebo regimen received at least one dose of study vaccine. Both regimens were well tolerated with no safety concerns. In stage 1, solicited local adverse events (mostly mild or moderate injection-site pain) were reported in 12 (28%) of 43 participants after Ad26.ZEBOV vaccination and in six (14%) participants after MVA-BN-Filo vaccination. In stage 2, solicited local adverse events were reported in 51 (17%) of 298 participants after Ad26.ZEBOV vaccination, in 58 (24%) of 246 after MVA-BN-Filo vaccination, in 17 (17%) of 102 after MenACWY vaccination, and in eight (9%) of 86 after placebo injection. In stage 1, solicited systemic adverse events were reported in 18 (42%) of 43 participants after Ad26.ZEBOV vaccination and in 17 (40%) after MVA-BN-Filo vaccination. In stage 2, solicited systemic adverse events were reported in 161 (54%) of 298 participants after Ad26.ZEBOV vaccination, in 107 (43%) of 246 after MVA-BN-Filo vaccination, in 51 (50%) of 102 after MenACWY vaccination, and in 39 (45%) of 86 after placebo injection. Solicited systemic adverse events in both stage 1 and 2 participants included mostly mild or moderate headache, myalgia, fatigue, and arthralgia. The most frequent unsolicited adverse event after the first dose was headache in stage 1 and malaria in stage 2. Malaria was the most frequent unsolicited adverse event after the second dose in both stage 1 and 2. No serious adverse event was considered related to the study vaccine, and no immediate reportable events were observed. In stage 1, the safety profile after the booster vaccination was not notably different to that observed after the first dose. Vaccine-induced humoral immune responses were observed in 41 (98%) of 42 stage 1 participants (geometric mean binding antibody concentration 4784 ELISA units [EU]/mL [95% CI 3736-6125]) and in 176 (98%) of 179 stage 2 participants (3810 EU/mL [3312-4383]) at 21 days after the second vaccination. INTERPRETATION: The Ad26.ZEBOV and MVA-BN-Filo vaccine regimen was well tolerated and immunogenic, with persistent humoral immune responses. These data support the use of this vaccine regimen for Ebola virus disease prophylaxis in adults. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.
Assuntos
Anticorpos Antivirais/sangue , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Imunogenicidade da Vacina , Vacinas de DNA/administração & dosagem , Vacinas Virais/administração & dosagem , Adulto , Anticorpos Antivirais/imunologia , República Democrática do Congo , Método Duplo-Cego , Vacinas contra Ebola/administração & dosagem , Ebolavirus/genética , Feminino , Humanos , Imunidade Humoral , Masculino , Serra Leoa , Vacinação/métodos , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Proteínas do Envelope Viral/administração & dosagem , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologiaRESUMO
Endemic Burkitt's lymphoma (eBL) has been linked to Epstein-Barr virus and holoendemic Plasmodium falciparum malaria. These co-infections, however, are insufficient to explain the non-random occurrence of Endemic Burkitt's lymphoma within Equatorial Africa. To explore whether this distribution could be explained by household characteristics and family environment, we conducted a case-control study using 41 hospitalized incident endemic Burkitt's lymphoma cases and 91 healthy controls identified through a population-based multistage cluster-sampling scheme in Nyanza Province, Kenya. In a multivariate analysis, odds ratios associated with having one, two, and three or more younger siblings compared with none were 0.28 (90% CI: 0.09, 0.83), 0.59 (90% CI: 0.16, 2.23) and 0.15 (90% CI: 0.03, 0.67) respectively, suggesting that children with endemic Burkitt's lymphoma were more likely than controls to be last-born. Children with endemic Burkitt's lymphoma were also more likely to live in non-monogamous families (OR=3.12, 90% CI:1.19, 8.17) and to have at least one deceased parent (OR=3.38, 90% CI: 1.18, 9.64). Household characteristics, especially sibship relationships, may contribute to endemic Burkitt's lymphoma and therefore warrant further study.
Assuntos
Linfoma de Burkitt/epidemiologia , Doenças Endêmicas , Características da Família , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Habitação , Humanos , Quênia/epidemiologia , Masculino , Razão de Chances , Fatores de RiscoRESUMO
BACKGROUND: The intestinal nematode Trichuris trichiura is among the most common causes of human infectious disease worldwide. As for other soil-transmitted nematodes, its reproductive success and thus prevalence and intensity of infection in a given area strongly depend on environmental conditions. Characterization of the influence of environmental factors can therefore aid to identify infection hot spots for targeted mass treatment. METHODOLOGY: We analyzed data from a cross-sectional survey including 6234 participants from nine distinct study sites in Mbeya region, Tanzania. A geographic information system was used to combine remotely sensed and individual data, which were analyzed using uni- and multivariable Poisson regression. Household clustering was accounted for and when necessary, fractional polynomials were used to capture non-linear relationships between T. trichiura infection prevalence and environmental variables. PRINCIPAL FINDINGS: T. trichiura infection was restricted to the Kyela site, close to Lake Nyasa with only very few cases in the other eight sites. The prevalence of T. trichiura infection in Kyela was 26.6% (95% confidence interval (CI) 23.9 to 29.6%). Multivariable models revealed a positive association of infection with denser vegetation (prevalence ratio (PR) per 0.1 EVI units = 2.12, CI 1.28 to 3.50) and inverse associations with rainfall (PR per 100 mm = 0.54, CI 0.44 to 0.67) and elevation (PR per meter = 0.89, CI 0.86 to 0.93) while adjusting for age and previous worm treatment. Slope of the terrain was modelled non-linearly and also showed a positive association with T. trichiura infection (p-value p<0.001). CONCLUSION/SIGNIFICANCE: Higher prevalences of T. trichiura infection were only found in Kyela, a study site characterized by denser vegetation, high rainfall, low elevation and flat terrain. But even within this site, we found significant influences of vegetation density, rainfall, elevation and slope on T. trichiura infection. The inverse association of rainfall with infection in Kyela is likely due to the fact, that rainfall in this site is beyond the optimum conditions for egg development. Our findings demonstrate that use of remotely sensed environmental data can aid to predict high-risk areas for targeted helminth control.
Assuntos
Tricuríase/epidemiologia , Trichuris/patogenicidade , Adolescente , Animais , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Tanzânia/epidemiologiaRESUMO
BACKGROUND: Malaria epidemics in highland areas of East Africa have caused considerable morbidity and mortality in the past two decades. Knowledge of "hotspot" areas of high malaria incidence would allow for focused preventive interventions in resource-poor areas, particularly if the hotspot areas can be discerned during non-epidemic periods and predicted by ecological factors. METHODS: To address this issue, spatial distribution of malaria incidence and the relationship of ecological factors to malaria incidence were assessed in the highland area of Kipsamoite, Kenya, from 2001-2004. RESULTS: Clustering of disease in a single geographic "hotspot" area occurred in epidemic and non-epidemic years, with a 2.6 to 3.2-fold increased risk of malaria inside the hotspot, as compared to outside the area (P < 0.001, all 4 years). Altitude and proximity to the forest were independently associated with increased malaria risk in all years, including epidemic and non-epidemic years. CONCLUSION: In this highland area, areas of high malaria risk are consistent in epidemic and non-epidemic years and are associated with specific ecological risk factors. Ongoing interventions in areas of ecological risk factors could be a cost-effective method of significantly reducing malaria incidence and blunting or preventing epidemics, even in the absence of malaria early warning systems. Further studies should be conducted to see if these findings hold true in varied highland settings.
Assuntos
Surtos de Doenças/estatística & dados numéricos , Ecossistema , Malária/epidemiologia , Altitude , Humanos , Quênia/epidemiologia , Análise Multivariada , Razão de Chances , Fatores de RiscoRESUMO
BACKGROUND: Annual mass treatment with ivermectin and albendazole is used to treat lymphatic filariasis in many African countries, including Tanzania. In areas where both diseases occur, it is unclear whether HIV co-infection reduces treatment success. METHODOLOGY: In a general population study in Southwest Tanzania, individuals were tested for HIV and circulating filarial antigen, an indicator of Wuchereria bancrofti adult worm burden, before the first and after 2 consecutive rounds of anti-filarial mass drug administration. PRINCIPLE FINDINGS: Testing of 2104 individuals aged 0-94 years before anti-filarial treatment revealed a prevalence of 24.8% for lymphatic filariasis and an HIV-prevalence of 8.9%. Lymphatic filariasis was rare in children, but prevalence increased in individuals above 10 years, whereas a strong increase in HIV was only seen above 18 years of age. The prevalence of lymphatic filariasis in adults above 18 years was 42.6% and 41.7% (p = 0.834) in HIV-negatives and-positives, respectively. Similarly, the HIV prevalence in the lymphatic filariasis infected (16.6%) and uninfected adult population (17.1%) was nearly the same. Of the above 2104 individuals 798 were re-tested after 2 rounds of antifilarial treatment. A significant reduction in the prevalence of circulating filarial antigen from 21.6% to 19.7% was found after treatment (relative drop of 8.8%, McNemar's exact p = 0.036). Furthermore, the post-treatment reduction of CFA positivity was (non-significantly) larger in HIV-positives than in HIV-negatives (univariable linear regression p = 0.154). CONCLUSION/SIGNIFICANCE: In an area with a high prevalence for both diseases, no difference was found between HIV-infected and uninfected individuals regarding the initial prevalence of lymphatic filariasis. A moderate but significant reduction in lymphatic filariasis prevalence and worm burden was demonstrated after two rounds of treatment with albendazole and ivermectin. Treatment effects were more pronounced in the HIV co-infected subgroup, indicating that the effectiveness of antifilarial treatment was not reduced by concomitant HIV-infection. Studies with longer follow-up time could validate the observed differences in treatment effectiveness.
Assuntos
Albendazol/uso terapêutico , Filariose Linfática/tratamento farmacológico , Filariose Linfática/epidemiologia , Filaricidas/uso terapêutico , Infecções por HIV/complicações , Ivermectina/uso terapêutico , Animais , Antígenos de Protozoários/sangue , Coinfecção/tratamento farmacológico , Humanos , Prevalência , Tanzânia/epidemiologia , Resultado do Tratamento , Wuchereria bancrofti/efeitos dos fármacos , Wuchereria bancrofti/isolamento & purificaçãoRESUMO
[This corrects the article DOI: 10.1371/journal.pntd.0004618.].
RESUMO
OBJECTIVE: African men who have sex with men often sell sex to men, and MSM who sell sex (MSM-SW) often also have female partners. We compared sexual risk behaviour of MSM-SW who were sexually active with female partners (bisexual MSW) to MSM-SW with only male partners (exclusive MSW). DESIGN: Descriptive behavioural study METHODS: : A novel, validated daily event and partner diary self-completed by 82 MSM who sold sex over a follow-up period of 42 days with weekly review. Cumulative individual counts of sex and condomless sex were compiled by partner characteristics. The incidence of specific partnerships and sex acts were compared within and between bisexual and exclusive MSW. RESULTS: Most (59%) MSM-SW reported female partners during follow-up. The majority of both male and female partners were cash-paying clients originating locally. Bisexual MSW reported a similar rate of condomless sex with male and female partners, but significantly fewer male partners than exclusive MSW. Bisexual MSW had lower HIV prevalence, were more likely to only report insertive anal sex roles, and reported lower frequencies of condomless receptive anal sex than exclusive MSW. CONCLUSION: Bisexually active male sex workers in coastal Kenya create HIV and other sexually transmitted infection transmission pathways to partners and clients in both MSM and heterosexual networks, but differed from exclusive MSW in having lower HIV acquisition and transmission risks. Epidemiological projection methods are liable to overestimate bridging potential of MSM-SW and MSM populations without account for systematic differences in risk within these populations.
Assuntos
Bissexualidade/estatística & dados numéricos , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Heterossexualidade/psicologia , Homossexualidade Masculina/estatística & dados numéricos , Profissionais do Sexo/estatística & dados numéricos , Adulto , Feminino , Humanos , Quênia/epidemiologia , Masculino , Prevalência , Assunção de Riscos , Autorrelato , Parceiros Sexuais , Adulto JovemRESUMO
BACKGROUND: With one quarter of the world population infected, the intestinal nematode Ascaris lumbricoides is one of the most common infectious agents, especially in the tropics and sub-tropics. Infection is caused by oral intake of eggs and can cause respiratory and gastrointestinal problems. To identify high risk areas for intervention, it is necessary to understand the effects of climatic, environmental and socio-demographic conditions on A. lumbricoides infection. METHODOLOGY: Cross-sectional survey data of 6,366 study participants in the Mbeya region of South-Western Tanzania were used to analyze associations between remotely sensed environmental data and A. lumbricoides infection. Non-linear associations were accounted for by using fractional polynomial regression, and socio-demographic and sanitary data were included as potential confounders. PRINCIPAL FINDINGS: The overall prevalence of A. lumbricoides infection was 6.8%. Our final multivariable model revealed a significant non-linear association between rainfall and A. lumbricoides infection with peak prevalences at 1740 mm of mean annual rainfall. Mean annual land surface temperature during the day was linearly modeled and negatively associated with A. lumbricoides infection (odds ratio (OR)â=â0.87, 95% confidence interval (CI)â=â0.78-0.97). Furthermore, age, which also showed a significant non-linear association (infection maximum at 7.7 years), socio-economic status (ORâ=â0.82, CIâ=â0.68-0.97), and latrine coverage around the house (ORâ=â0.80, CIâ=â0.67-0.96) remained in the final model. CONCLUSIONS: A. lumbricoides infection was associated with environmental, socio-demographic and sanitary factors both in uni- and multivariable analysis. Non-linear analysis with fractional polynomials can improve model fit, resulting in a better understanding of the relationship between environmental conditions and helminth infection, and more precise predictions of high prevalence areas. However, socio-demographic determinants and sanitary conditions should also be considered, especially when planning public health interventions on a smaller scale, such as the community level.
Assuntos
Ascaríase/epidemiologia , Ascaris lumbricoides/fisiologia , Adolescente , Adulto , Análise de Variância , Animais , Ascaríase/parasitologia , Ascaríase/transmissão , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Chuva , Fatores Socioeconômicos , Tanzânia/epidemiologia , TemperaturaRESUMO
BACKGROUND: Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics. Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control. METHODOLOGY: Cross-sectional interview data and stool samples from 6,375 participants from nine different sites in Mbeya region, south-western Tanzania, were collected as part of a cohort study. Hookworm infection was assessed by microscopy of duplicate Kato-Katz thick smears from one stool sample from each participant. A geographic information system was used to obtain remotely sensed environmental data such as land surface temperature (LST), vegetation cover, rainfall, and elevation, and combine them with hookworm infection data and with socio-demographic and behavioral data. Uni- and multivariable logistic regression was performed on sites separately and on the pooled dataset. PRINCIPAL FINDINGS: Univariable analyses yielded significant associations for all ecological variables. Five ecological variables stayed significant in the final multivariable model: population density (odds ratio (OR)â=â0.68; 95% confidence interval (CI)â=â0.63-0.73), mean annual vegetation density (ORâ=â0.11; 95% CIâ=â0.06-0.18), mean annual LST during the day (ORâ=â0.81; 95% CIâ=â0.75-0.88), mean annual LST during the night (ORâ=â1.54; 95% CIâ=â1.44-1.64), and latrine coverage in household surroundings (ORâ=â1.02; 95% CIâ=â1.01-1.04). Interaction terms revealed substantial differences in associations of hookworm infection with population density, mean annual enhanced vegetation index, and latrine coverage between the two sites with the highest prevalence of infection. CONCLUSION/SIGNIFICANCE: This study supports previous findings that remotely sensed data such as vegetation indices, LST, and elevation are strongly associated with hookworm prevalence. However, the results indicate that the influence of environmental conditions can differ substantially within a relatively small geographic area. The use of large-scale associations as a predictive tool on smaller scales is therefore problematic and should be handled with care.
Assuntos
Infecções por Uncinaria/epidemiologia , Topografia Médica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Fezes/parasitologia , Feminino , Humanos , Lactente , Recém-Nascido , Entrevistas como Assunto , Masculino , Microscopia , Pessoa de Meia-Idade , Prevalência , Tanzânia/epidemiologia , Adulto JovemRESUMO
"Background: Malaria epidemics in highland areas of East Africa have caused considerable morbidity and mortality in the past two decades. Knowledge of ""hotspot"" areas of high malaria incidence would allow for focused preventive interventions in resource-poor areas; particularly if the hotspot areas can be discerned during non-epidemic periods and predicted by ecological factors. Methods:To address this issue; spatial distribution of malaria incidence and the relationship of ecological factors to malaria incidence were assessed in the highland area of Kipsamoite; Kenya; from 001-2004. Results: Clustering of disease in a single geographic ""hotspot"" area occurred in epidemic and non-epidemic years; with a 2.6 to 3.2-fold increased risk of malaria inside the hotspot; as compared to outside the area (P 0.001; all 4 years). Altitude and proximity to the forest were independently associated with increased malaria risk in all years; including epidemic and non-epidemic years. Conclusion: In this highland area; areas of high malaria risk are consistent in epidemic and non-epidemic years and are associated with specific ecological risk factors. Ongoing interventions in areas of ecological risk factors could be a cost-effective method of significantly reducing malaria incidence and blunting or preventing epidemics; even in the absence of malaria early warning systems. Further studies should be conducted to see if these findings hold true in varied highland settings."